2. Academic Validation
  3. Structure and Physiological Regulation of AMPK

Structure and Physiological Regulation of AMPK

  • Int J Mol Sci. 2018 Nov 9;19(11):3534. doi: 10.3390/ijms19113534.
Yan Yan 1 2,  X Edward Zhou 3,  H Eric Xu 4 5,  Karsten Melcher 6
Affiliations

Affiliations

  • 1 Center for Cancer and Cell Biology, Van Andel Research Institute, 333 Bostwick Ave. N.E., Grand Rapids, MI 49503, USA. [email protected].
  • 2 VARI/SIMM Center, Center for Structure and Function of Drug Targets, CAS-Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. [email protected].
  • 3 Center for Cancer and Cell Biology, Van Andel Research Institute, 333 Bostwick Ave. N.E., Grand Rapids, MI 49503, USA. [email protected].
  • 4 Center for Cancer and Cell Biology, Van Andel Research Institute, 333 Bostwick Ave. N.E., Grand Rapids, MI 49503, USA. [email protected].
  • 5 VARI/SIMM Center, Center for Structure and Function of Drug Targets, CAS-Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. [email protected].
  • 6 Center for Cancer and Cell Biology, Van Andel Research Institute, 333 Bostwick Ave. N.E., Grand Rapids, MI 49503, USA. [email protected].
PMID: 30423971 DOI: 10.3390/ijms19113534
Abstract

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a heterotrimeric αβγ complex that functions as a central regulator of energy homeostasis. Energy stress manifests as a drop in the ratio of adenosine triphosphate (ATP) to AMP/ADP, which activates AMPK's kinase activity, allowing it to upregulate ATP-generating catabolic pathways and to reduce energy-consuming catabolic pathways and cellular programs. AMPK senses the cellular energy state by competitive binding of the three adenine nucleotides AMP, ADP, and ATP to three sites in its γ subunit, each, which in turn modulates the activity of AMPK's kinase domain in its α subunit. Our current understanding of adenine nucleotide binding and the mechanisms by which differential adenine nucleotide occupancies activate or inhibit AMPK activity has been largely informed by crystal structures of AMPK in different activity states. Here we provide an overview of AMPK structures, and how these structures, in combination with biochemical, biophysical, and mutational analyses provide insights into the mechanisms of adenine nucleotide binding and AMPK activity modulation.

Keywords

AID; AMPK; CBS; CaMKK2; LKB1; activation loop; energy metabolism; α-linker; αRIM; β-linker.

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